Protein marker for Parkinson's disease diagnosis and application thereof

Abstract

The invention relates to a protein marker for Parkinson's disease diagnosis and application thereof, and belongs to the technical field of biological medicine. The invention finds that the Talin-1 protein expression in a Parkinson's disease patient is reduced, further explores the linear relationship between the Talin-1 protein level and the Parkinson's disease, and finds that the Talin-1 protein level in serum and the Parkinson's disease have an obvious linear relationship, the risk of the Parkinson's disease is gradually reduced along with the increase of the Talin-1 protein level in the serum, and a threshold effect exists. Therefore, it is speculated that the Talin-1 protein not only can be used as a marker for diagnosing the Parkinson's disease, but also can be used as a drug target for preventing the Parkinson's disease. The ROC curve further proves that the Talin-1 protein level in the serum has good diagnostic value on Parkinson's disease.

Description

Technical Field

[0001] The present invention relates to the field of biomedical technology, and in particular to a protein marker for Parkinson's disease diagnosis and application thereof. Background Art

[0002] Parkinson's disease is a chronic, progressive neurodegenerative disease characterized by motor dysfunction, including tremor, rigidity, bradykinesia, and postural balance disorders. Globally, the incidence and prevalence of Parkinson's disease are increasing year by year, and this trend is particularly evident as the population ages. With the continuous advancement of medical technology and the deepening of research, the application of early detection, early diagnosis, and early treatment in the field of Parkinson's disease will be more extensive and in-depth. On the one hand, the early detection rate and diagnostic accuracy of Parkinson's disease can be improved through the continuous improvement of diagnostic standards and the application of modern medical technology; on the other hand, the formulation and implementation of comprehensive treatment strategies will be more personalized and precise. At the same time, the development of new drugs and therapies will provide patients with more effective treatment options. Therefore, the early and effective identification of Parkinson's disease can effectively improve the cure rate. In addition, in addition to treatment, the prevention of Parkinson's disease is more important. Effective and rapid identification of high-risk individuals is the key to the prevention of Parkinson's disease. Early biomarkers of Parkinson's disease mainly include the following aspects: (1) Neurochemical markers: Dysfunction of the dopamine system is the core pathophysiological process of Parkinson's disease. Therefore, changes in the levels of dopamine and its metabolites can be regarded as early biomarkers. (2) Imaging markers: In neuroimaging examinations, some features observed can also serve as early biomarkers of Parkinson's disease. For example, using magnetic resonance imaging (MRI), structural changes in specific areas of the brain can be observed, including a decrease in the volume of the substantia nigra and striatum, which is usually an early manifestation of Parkinson's disease. (3) Genetic markers: Some Parkinson's disease patients have specific gene mutations, which can serve as genetic markers of Parkinson's disease. For example, mutations in the α-synuclein gene (SNCA) or other related genes may increase the risk of Parkinson's disease. (4) Hematological markers: α-synuclein and its phosphorylated form, uric acid as a metabolite, play an important role in oxidative stress and neuroprotection in PD. Exosomes are a potential carrier of PD biomarkers. Their detection in the blood may provide a new breakthrough for early diagnosis. The pathogenic mechanism of Parkinson's disease is complex, and the biomarkers are correspondingly more complex. So far, there is no single marker that can well identify Parkinson's disease. More biomarkers need to be discovered, and combined use may be one of the directions.

[0003] Talin-1 protein is a cytoskeleton-related protein that participates in the interaction between cells and the extracellular matrix by interacting with integrins on the cell membrane. Talin-1 protein has multiple functions in cells, including cell adhesion, signal transduction, migration and growth. In-depth research on Talin-1 protein will help reveal the mysteries of cell physiological and pathological processes and provide new possibilities for the diagnosis and treatment of related diseases. Basic research has confirmed that in neurons, Talin-1 protein is involved in the formation and maintenance of synapses and the release of neurotransmitters, thereby affecting the normal transmission of neurotransmitters. Talin-1 protein may affect the function and number of mitochondria by regulating processes such as mitochondrial membrane potential and mitochondrial autophagy, thereby affecting the survival and function of neurons. Clinical studies have found that Talin-1 protein is significantly associated with myocardial infarction, cancer, and osteoporosis, but there is no clinical research evidence on the association between Talin-1 protein and Parkinson's disease. Summary of the invention

[0004] Therefore, the technical problem to be solved by the present invention is to overcome the problem in the prior art of lacking a marker that can well diagnose Parkinson's disease.

[0005] In order to solve the above technical problems, the present invention provides a protein marker for Parkinson's diagnosis and its application. The present invention found that the expression of Talin-1 protein was reduced in Parkinson's patients, and further explored the linear relationship between Talin-1 protein level and Parkinson's disease. It was found that there was a significant linear relationship between the Talin-1 protein level in serum and Parkinson's disease. As the Talin-1 protein level in serum increased, the risk of Parkinson's disease gradually decreased, and there was a threshold effect. Therefore, it is speculated that Talin-1 protein can not only be used as a marker for diagnosing Parkinson's, but also may be a drug target for preventing Parkinson's. The ROC curve further proved that the Talin-1 protein level in serum has a good diagnostic value for Parkinson's.

[0006] The first object of the present invention is to provide a protein marker for diagnosing Parkinson's disease, wherein the marker is Talin-1 protein.

[0007] Furthermore, the amino acid sequence of the Talin-1 protein is shown in SEQ ID NO.1.

[0008] Furthermore, the amino acid sequence of SEQ ID NO.1 is as follows:

[0009]

[0010] The second object of the present invention is to provide an application of the above protein marker in a Parkinson's disease diagnosis kit.

[0011] The third object of the present invention is to provide a Parkinson's disease diagnostic kit, wherein the Parkinson's disease diagnostic kit uses Talin-1 protein as a marker.

[0012] Furthermore, the test sample of the Parkinson's disease diagnosis kit is serum.

[0013] Furthermore, the Parkinson's disease diagnostic kit includes a reagent for detecting the content of Talin-1 protein.

[0014] Furthermore, the Parkinson's disease diagnostic kit includes antibodies that can specifically recognize and bind to Talin-1 protein.

[0015] Furthermore, the Parkinson's disease diagnosis kit comprises an enzyme-linked immunosorbent assay component, and the enzyme-linked immunosorbent assay component comprises a detection plate, a buffer solution and a Talin-1 protein standard sample.

[0016] The fourth object of the present invention is to provide a Parkinson's disease treatment target, wherein the Parkinson's disease treatment target is Talin-1 protein.

[0017] The fifth object of the present invention is to provide a use of a Talin-1 protein agonist in the preparation of a drug for preventing or treating Parkinson's disease.

[0018] Beneficial effects of the present invention:

[0019] A protein marker for Parkinson's disease diagnosis and its application described in the present invention. The present invention found that the expression of Talin-1 protein was reduced in Parkinson's patients, and further explored the linear relationship between Talin-1 protein level and Parkinson's disease. It was found that there was a significant linear relationship between the Talin-1 protein level in serum and Parkinson's disease. As the Talin-1 protein level in serum increased, the risk of Parkinson's disease gradually decreased, and there was a threshold effect. Therefore, it is speculated that Talin-1 protein can not only be used as a marker for diagnosing Parkinson's disease, but also may be a drug target for preventing Parkinson's disease. The ROC curve further proved that the Talin-1 protein level in serum has a good diagnostic value for Parkinson's disease. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] In order to make the content of the present invention more clearly understood, the present invention is further described in detail below according to specific embodiments of the present invention in conjunction with the accompanying drawings, wherein

[0021] Figure 1 This is the screening process of the sample in Example 1 of the present invention;

[0022] Figure 2 is the expression level of Talin-1 protein in the serum of case group, unselected control group and matched control group;

[0023] Figure 3 is the RCS curve of serum Talin-1 protein and Parkinson's disease risk;

[0024] Figure 4 This is the ROC curve of Talin-1 protein for Parkinson's disease. DETAILED DESCRIPTION

[0025] The present invention is further described below in conjunction with the accompanying drawings and specific embodiments so that those skilled in the art can better understand the present invention and implement it, but the embodiments are not intended to limit the present invention.

[0026] Example 1: Sample screening

[0027] like Figure 1 As shown in the figure, 415 Parkinson's disease patients were collected in the Second Affiliated Hospital of Soochow University as the case group, and 1907 people without Parkinson's disease were selected from the community residents in Gusu District, Suzhou City to form a non-selected control group. In addition, 415 healthy people were selected according to age and gender as matching conditions to form a matched control group. The general characteristics of the research subjects in each group are shown in the table below. Compared with healthy controls, Parkinson's disease patients had higher rates of smoking and drinking, but lower rates of diabetes and hypertension.

[0028] Table 1 Clinical characteristics of the case group and control group screened in Example 1

[0029]

[0030] Example 2: Predicted effect of Talin-1 protein

[0031] Use ELISA kit ( Bionovation Inc., Houston, USA. Catalog: E-EL-H6072) was used to detect the Talin-1 protein level in the serum of Parkinson's disease patients, unselected controls and matched controls by ELISA. The results are as follows Figure 2 As shown in the data, the median levels of serum Talin-1 protein in Parkinson's disease patients, non-selected controls and matched controls were 23.19 (17.76-31.25) pg / mL, 81.26 (64.34-99.70) pg / mL and 83.55 (65.61-104.91) pg / mL, respectively. Compared with the healthy control group, the serum Talin-1 protein level in Parkinson's disease patients was significantly reduced (P<0.001).

[0032] After further correction of traditional risk factors such as age, gender, marital status, education level, smoking, drinking, diabetes and hypertension history, the risk of Parkinson's disease decreased by 13% for every 1pg / mL increase in serum Talin-1 protein level. The results are shown in Table 2. The RCS curve further showed that there was a significant linear relationship between serum Talin-1 protein level and Parkinson's disease. With the increase of serum Talin-1 protein level, the risk of Parkinson's disease gradually decreased, but there was a threshold effect ( Figure 3 ). This indicates that when serum Talin-1 protein increases to a certain level or reaches a non-deficient level, the risk of Parkinson's disease no longer changes. It is speculated that Talin-1 protein can not only be used as a marker for diagnosing Parkinson's disease, but also may be a drug target for preventing Parkinson's disease.

[0033] Table 2 Relationship between serum Talin-1 protein and Parkinson's disease prevalence

[0034]

[0035] The ROC analysis results showed that ( Figure 4 ), serum Talin-1 protein level has a good diagnostic value for Parkinson's disease, with an area under the ROC curve of 0.98 and 95% CI of 0.97-0.99.

[0036] Obviously, the above embodiments are merely examples for clear explanation and are not intended to limit the implementation methods. For those skilled in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the implementation methods here. The obvious changes or modifications derived from these are still within the protection scope of the invention.

Claims

1. A protein marker for Parkinson's disease diagnosis, characterized in that: The protein marker is Talin-1 protein.

2. The protein marker according to claim 1, characterized in that The amino acid sequence of the Talin-1 protein is shown in SEQ ID NO.

1.

3. Use of the protein marker according to claim 1 or 2 in preparing a Parkinson's disease diagnostic kit.

4. A Parkinson's disease diagnostic kit, characterized in that: The Parkinson's disease diagnostic kit uses Talin-1 protein as a marker.

5. The Parkinson's disease diagnostic kit according to claim 4, characterized in that: The detection sample of the Parkinson's disease diagnosis kit is serum.

6. The Parkinson's disease diagnostic kit according to claim 4, characterized in that: The Parkinson's disease diagnostic kit comprises a reagent for detecting the content of Talin-1 protein.

7. The Parkinson's disease diagnostic kit according to claim 4, characterized in that: The Parkinson's disease diagnostic kit comprises an antibody that can specifically recognize and bind to Talin-1 protein.

8. The Parkinson's disease diagnostic kit according to claim 7, characterized in that: The Parkinson's disease diagnosis kit comprises an enzyme-linked immunosorbent assay component, which comprises a detection plate, a buffer solution and a Talin-1 protein standard sample.

9. A Parkinson's disease treatment target, characterized in that: The Parkinson's disease treatment target is Talin-1 protein.

10. Application of Talin-1 protein agonist in the preparation of drugs for the prevention or treatment of Parkinson's disease.

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